Antiviral Drugs Against Severe Fever With Thrombocytopenia Syndrome Virus Infection

Takayama-Ito, Mutsuyo; Saijo, Masayuki

doi:10.3389/fmicb.2020.00150

Cited by 56 publications

(54 citation statements)

References 78 publications

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“…FPV was also tested as a drug in severe fever with thrombocytopenia syndrome (SFTS), which is an emerging tick-borne infectious disease caused by the novel bunyavirus-SFTS virus (SFTSV) [ 68 , 72 ].…”

Section: Effectiveness Of Fpv In Other Human Rna Infectionsmentioning

confidence: 99%

Favipiravir in Therapy of Viral Infections

Łagocka

Dziedziejko

Kłos

et al. 2021

JCM

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Favipiravir (FPV) is a novel antiviral drug acting as a competitive inhibitor of RNA-dependent RNA polymerase (RdRp), preventing viral transcription and replication. FPV was approved in Japan in 2014 for therapy of influenza unresponsive to standard antiviral therapies. FPV was also used in the therapy of Ebola virus disease (EVD) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this review, we discuss the mechanisms of action, pharmacokinetic parameters, toxicity, and adverse effects of FPV, as well as clinical studies evaluating the use of FPV in the therapy of influenza virus (IV) infection, EVD, and SARS-CoV-2 infection, along with its effectiveness in treating other human RNA infections.

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Section: Effectiveness Of Fpv In Other Human Rna Infectionsmentioning

confidence: 99%

Favipiravir in Therapy of Viral Infections

Łagocka

Dziedziejko

Kłos

et al. 2021

JCM

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“…Since SFTSV was first identified in China in 2010, SFTS cases have been identified in China, Japan, South Korea, Vietnam, and Taiwan [ 2 ]. The fatality rate of SFTS is high (6–32%) but more specific or effective treatments or vaccines have not been developed yet [ 3 ]. Thus, SFTS is listed in the World Health Organization Prioritized Pathogens, which pose major public health risks and further research and development are needed [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Pathogenicity of severe fever with thrombocytopenia syndrome virus in mice regulated in type I interferon signaling

Park

Choi

et al. 2020

Lab Anim Res

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Severe fever with thrombocytopenia syndrome (SFTS) is an emerging zoonotic disease, which causes high fever, thrombocytopenia, and death in humans and animals in East Asian countries. The pathogenicity of SFTS virus (SFTSV) remains unclear. We intraperitoneally infected three groups of mice: wild-type (WT), mice treated with blocking anti-type I interferon (IFN)-α receptor antibody (IFNAR Ab), and IFNAR knockout (IFNAR−/−) mice, with four doses of SFTSV (KH1, 5 × 105 to 5 × 102 FAID50). The WT mice survived all SFTSV infective doses. The IFNAR Ab mice died within 7 days post-infection (dpi) with all doses of SFTSV except that the mice were infected with 5 × 102 FAID50 SFTSV. The IFNAR−/− mice died after infection with all doses of SFTSV within four dpi. No SFTSV infection caused hyperthermia in any mice, whereas all the dead mice showed hypothermia and weight loss. In the WT mice, SFTSV RNA was detected in the eyes, oral swabs, urine, and feces at 5 dpi. Similar patterns were observed in the IFNAR Ab and IFNAR−/− mice after 3 dpi, but not in feces. The IFNAR Ab mice showed viral shedding until 7 dpi. The SFTSV RNA loads were higher in organs of the IFNAR−/− mice compared to the other groups. Histopathologically, coagulation necrosis and mononuclear inflammatory cell infiltration in the liver and white pulp atrophy in the spleen were seen as the main lesions in the IFN signaling lacking mice. Immunohistochemically, SFTSV antigens were mainly detected in the marginal zone of the white pulp of the spleen in all groups of mice, but more viral antigens were observed in the spleen of the IFNAR−/− mice. Collectively, the IFN signaling-deficient mice were highly susceptible to SFTSV and more viral burden could be demonstrated in various excreta and organs of the mice when IFN signaling was inhibited.

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“…Intriguingly, loperamide has shown to inhibit multiplications of several human coronaviruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which also cause diarrhea Viruses 2021, 13, 869 2 of 12 in humans [12,13]. In addition, loperamide was proposed to exert its antidiarrheal effect by blocking calcium channels [14] and several calcium channel blockers have been reported to inhibit the SFTSV replication in vivo and in vitro [11]. These findings encourage efforts to investigate the potential clinical use of loperamide to reduce viral load and simultaneously to alleviate diarrhea in SFTS patients.…”

Section: Introductionmentioning

confidence: 99%

“…It is critical to develop such prophylaxis/treatment, and elucidation of the virus replication mechanism could help determine treatment strategies. Despite the lack of established treatments against SFTS, several compounds, including Food and Drug Administration (FDA)-approved drugs, have been reported to inhibit SFTSV replication both in vivo and in vitro [ 11 ]. In this study, we focused on the FDA-approved antidiarrheal drug loperamide because diarrhea is a prominent symptom of SFTS [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Loperamide Inhibits Replication of Severe Fever with Thrombocytopenia Syndrome Virus

Urata

Yasuda

Iwasaki

2021

Viruses

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Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease caused by the SFTS virus (SFTSV). SFTS is mainly prevalent in East Asia. It has a mortality rate of up to 30%, and there is no approved treatment against the disease. In this study, we evaluated the effect of loperamide, an antidiarrheal and antihyperalgesic agent, on the propagation of SFTSV in a cell culture system. Methods: SFTSV-infected human cell lines were exposed to loperamide, and viral titers were evaluated. To clarify the mode of action of loperamide, several chemical compounds having shared targets with loperamide were used. Calcium imaging was also performed to understand whether loperamide treatment affected calcium influx. Results: Loperamide inhibited SFTSV propagation in several cell lines. It inhibited SFTSV in the post-entry step and restricted calcium influx into the cell. Furthermore, nifedipine, a calcium channel inhibitor, also blocked post-entry step of SFTSV infection. Conclusions: Loperamide inhibits SFTSV propagation mainly by restraining calcium influx into the cytoplasm. This indicates that loperamide, a Food and Drug Administration (FDA)-approved drug, has the potential for being used as a treatment option against SFTS.

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Antiviral Drugs Against Severe Fever With Thrombocytopenia Syndrome Virus Infection

Cited by 56 publications

References 78 publications

Favipiravir in Therapy of Viral Infections

Favipiravir in Therapy of Viral Infections

Pathogenicity of severe fever with thrombocytopenia syndrome virus in mice regulated in type I interferon signaling

Loperamide Inhibits Replication of Severe Fever with Thrombocytopenia Syndrome Virus

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